The overall ovjective of this integrated group of research studies is a more comprehensive understanding of the pathophysiology of unipolar and bipolar affective disorder, particularly with regard to the complex interrelationships among clinical phenomenology, diagnosis, biological variables, and pharmacologic response. The studies are both cross-sectional and longitudinal; drug trials and double-blind. Integration of the inpatient and outpatient units has advanced, focusing on a brief pretreatment inpatient evaluation of patients with a variety of endogenous and non-endogenous depressive snydromes, followed by outpatient treatment. Meanwhile, longitudinal inpatient studies of endogenous depression, mania, and rapid-cycling bipolar illness continue. Major projects include the study of circadian and seasonal rhythms, neuroendocrine substances and monoamine neurotransmitters and their metabolites, both during untreated affective episodes and following specific treatment. The primary treatment modalities include (1) environmental manipulations, such as sleep deprivation or sleep shifts; (2) tricyclic antidepressants showing specificity for given neurotransmitter systems; and (3) electroconclusive therapy (ECT).